A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia

Abstract

Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART).

Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months.

Results: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50).

Conclusions: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes.

Clinical trials registration: This trial is registered at https://clinicaltrials.gov (NCT02682810).

Keywords: early infant diagnosis of HIV; pediatric HIV low- and middle income country; point of care diagnosis; prevention of mother to child HIV transmission.

Figure 1.

Participant flow diagram. ^aProtocol version 5.0 (15 August 2016) excluded twins and higher-order multiples; none of the 3 sets of twins randomized were HIV positive. ^bIncludes 2 infants who died and 2 infants who were lost to follow-up prior to confirmatory testing. Abbreviations: ART, antiretroviral therapy; EID, early infant diagnosis; HIV, human immunodeficiency virus.

Figure 2.

Time to result by randomization group. ^aThe enhanced SOC (blue line) and offsite SOC without safety net (green line) represent time-to-result for the same infants (those randomized to enhanced SOC). Follow-up time for the offsite SOC without safety net (green line) was censored at 90 days after the initial blood draw. Abbreviations: EID, early infant diagnosis; POC, point of care; SOC, standard of care.

Figure 3.

Time-to-ART initiation among infants with HIV. Infants who died or were lost to follow-up remained in the denominator for this analysis. The numbers below the cumulative probability curves represent the number of infants at risk (ie, those infants with HIV who had not yet initiated ART). Abbreviations: ART, antiretroviral therapy; EID, early infant diagnosis; HIV, human immunodeficiency virus; POC, point of care; SOC, standard of care.

Figure 4.

Probability of death and follow-up loss among infants with HIV. The numbers below the cumulative probability curves represent the number of infants at risk. In panel A, follow-up is right-censored at the last study-related contact for each infant; and in panel B, follow-up loss is counted as an event. Abbreviations: EID, early infant diagnosis; HIV, human immunodeficiency virus; POC, point of care; SOC, standard of care.